Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
Background:Although TB health promotion directed at policy makers and healthcare workers(HCWs)is considered important to tuberculosis(TB)control,no indicators currently assess the impact of such promotional activities...Background:Although TB health promotion directed at policy makers and healthcare workers(HCWs)is considered important to tuberculosis(TB)control,no indicators currently assess the impact of such promotional activities.This article is the second in a series of papers that seek to establish a framework of behavioral indicators for outcome evaluation of TB health promotion,using the Delphi method.In the first article,we sought to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients.The objective of this second article is to present an indicator framework that can be used to assess behavioral outcomes of TB health promotion directed at policy makers and HCWs.Methods:A two-round,modified Delphi method was used to establish the indicators.Sixteen experts who were knowledgeable and experienced in the field of TB control were consulted in Delphi surveys.A questionnaire was developed following 4 steps,and involved ranking indicators on a five-point Likert scale.The consensus level was 70%.Median,mode,and Coefficient of variation(CV)were used to describe expert responses.An authority coefficient(Cr)was used to assess the degree of each expert’s authority.Results:Consensus was achieved following the two survey rounds and several iterations among the experts.For TB health-promotion activities directed at policymakers,the experts reached consensus on 2 domains(“Resource inputs”and“Policymaking and monitoring behaviors”),4 subdomains(“Human resources”among others),and 13 indicators(“Human resources per 100,000 person”among others).For TB health-promotion activities directed at HCWs,the experts reached consensus on 5 domains(“Self-protective behaviors”among others),6 sub-domains(“Preventing infection”among others),and 15 indicators(“Average hours of daily workplace disinfection by ultraviolet radiation”among others).Conclusions:This study identified a conceptual framework of core behavioral indicators to evaluate TB health-promotion activities directed at policymakers and HCWs involved in TB control.Validation in other parts of the world could lead to global consensus on behavioral indicators to evaluate TB health promotion targeted at policymakers and HCWs.展开更多
Background Tuberculosis(TB)is one of the top 10 causes of death in the world.Since Directly Observed Therapy(DOT)as a core strategy for the global TB control are not applicable to all types of TB patients,and self-man...Background Tuberculosis(TB)is one of the top 10 causes of death in the world.Since Directly Observed Therapy(DOT)as a core strategy for the global TB control are not applicable to all types of TB patients,and self-management of TB patients(SMTP)as a patient-centered supervision type is a supplement to DOT and can improve TB case management.However,the factors related to SMTP are complex and need more study.This study aimed at identifying the determinants of SMTP and examining the direct/indirect effects of these determinants.Methods The purposive sampling technique was used to select study sites and participants were recruited from the study sites by the consecutive sampling method.The PRECEDE model was used as the framework to analyze the determinants of SMTP.The responses of TB patients were acquired via a questionnaire survey for data collection.A Pearson correlation analysis was used to define the relationship between the predisposing,enabling,reinforcing factors with SMTP behaviors.A regression-based path analysis was used to determine the action paths of the predisposing,enabling,and reinforcing factors on SMTP behaviors.Results The predisposing(TB knowledge),enabling[health education and healthcare workers(HCWs)support],reinforcing factors(family support)had significant positive correlations with SMTP behaviors(P<0.05).The predisposing,enabling,reinforcing factors were positively correlated with each other(r=0.123‒0.918,P<0.05),except for family support and HCWs support.The predisposing factors(TB knowledge,β=0.330)and the enabling factors(HCWs support,β=0.437)had direct effects on SMTP behaviors.The enabling factors(health education and HCWs support)and the reinforcing factors(family support)had indirect effects on SMTP behaviors.Conclusions This study revealed the effects and action path of TB knowledge,health education,HCWs support,and family support on SMTP behaviors via a path analysis.Assessing patient’s needs for SMTP along with promoting effective TB health education and providing firm support from HCWs and family members are potential strategies to promote SMTP behaviors.展开更多
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
基金This project was funded by the National Natural Science Foundation of China(Award#81001297).The authors would like to thank participants on the expert panel for the discussion during the process of proposing the framework.The authors would like to acknowledge Professor Shenglan Tang of the Institute of Global Health,Duke University for his comments on the paper.
文摘Background:Although TB health promotion directed at policy makers and healthcare workers(HCWs)is considered important to tuberculosis(TB)control,no indicators currently assess the impact of such promotional activities.This article is the second in a series of papers that seek to establish a framework of behavioral indicators for outcome evaluation of TB health promotion,using the Delphi method.In the first article,we sought to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients.The objective of this second article is to present an indicator framework that can be used to assess behavioral outcomes of TB health promotion directed at policy makers and HCWs.Methods:A two-round,modified Delphi method was used to establish the indicators.Sixteen experts who were knowledgeable and experienced in the field of TB control were consulted in Delphi surveys.A questionnaire was developed following 4 steps,and involved ranking indicators on a five-point Likert scale.The consensus level was 70%.Median,mode,and Coefficient of variation(CV)were used to describe expert responses.An authority coefficient(Cr)was used to assess the degree of each expert’s authority.Results:Consensus was achieved following the two survey rounds and several iterations among the experts.For TB health-promotion activities directed at policymakers,the experts reached consensus on 2 domains(“Resource inputs”and“Policymaking and monitoring behaviors”),4 subdomains(“Human resources”among others),and 13 indicators(“Human resources per 100,000 person”among others).For TB health-promotion activities directed at HCWs,the experts reached consensus on 5 domains(“Self-protective behaviors”among others),6 sub-domains(“Preventing infection”among others),and 15 indicators(“Average hours of daily workplace disinfection by ultraviolet radiation”among others).Conclusions:This study identified a conceptual framework of core behavioral indicators to evaluate TB health-promotion activities directed at policymakers and HCWs involved in TB control.Validation in other parts of the world could lead to global consensus on behavioral indicators to evaluate TB health promotion targeted at policymakers and HCWs.
文摘Background Tuberculosis(TB)is one of the top 10 causes of death in the world.Since Directly Observed Therapy(DOT)as a core strategy for the global TB control are not applicable to all types of TB patients,and self-management of TB patients(SMTP)as a patient-centered supervision type is a supplement to DOT and can improve TB case management.However,the factors related to SMTP are complex and need more study.This study aimed at identifying the determinants of SMTP and examining the direct/indirect effects of these determinants.Methods The purposive sampling technique was used to select study sites and participants were recruited from the study sites by the consecutive sampling method.The PRECEDE model was used as the framework to analyze the determinants of SMTP.The responses of TB patients were acquired via a questionnaire survey for data collection.A Pearson correlation analysis was used to define the relationship between the predisposing,enabling,reinforcing factors with SMTP behaviors.A regression-based path analysis was used to determine the action paths of the predisposing,enabling,and reinforcing factors on SMTP behaviors.Results The predisposing(TB knowledge),enabling[health education and healthcare workers(HCWs)support],reinforcing factors(family support)had significant positive correlations with SMTP behaviors(P<0.05).The predisposing,enabling,reinforcing factors were positively correlated with each other(r=0.123‒0.918,P<0.05),except for family support and HCWs support.The predisposing factors(TB knowledge,β=0.330)and the enabling factors(HCWs support,β=0.437)had direct effects on SMTP behaviors.The enabling factors(health education and HCWs support)and the reinforcing factors(family support)had indirect effects on SMTP behaviors.Conclusions This study revealed the effects and action path of TB knowledge,health education,HCWs support,and family support on SMTP behaviors via a path analysis.Assessing patient’s needs for SMTP along with promoting effective TB health education and providing firm support from HCWs and family members are potential strategies to promote SMTP behaviors.
